CCSS Neurology Committee Report: 6/08 · CCSS Neurology Committee Report: 6/08 Roger J. Packer, MD...
Transcript of CCSS Neurology Committee Report: 6/08 · CCSS Neurology Committee Report: 6/08 Roger J. Packer, MD...
CCSS Neurology Committee Report: 6/08CCSS Neurology Committee Report: 6/08
Roger J. Packer, MDRoger J. Packer, MDExecutive Director Neuroscience and Behavioral MedicineExecutive Director Neuroscience and Behavioral Medicine
Chairman, NeurologyChairman, NeurologyDirector, Brain Tumor InstituteDirector, Brain Tumor Institute
ChildrenChildren’’s National Medical Centers National Medical CenterWashington, DCWashington, DC
Neurology Committee: CCSSNeurology Committee: CCSSWas until 2007 component of Neuropsychology/Psychology/Was until 2007 component of Neuropsychology/Psychology/
Neurology CommitteeNeurology Committee
Joint direction Joint direction (co(co--chairs: L. Zeltzer/R. Packer)chairs: L. Zeltzer/R. Packer)-- clear overlapclear overlap-- unclear focusunclear focus
OpportunitiesOpportunities::-- missed missed ““neurologicneurologic”” complications/sequelaecomplications/sequelae-- missed neurosensory issuesmissed neurosensory issues-- primarily new cohortprimarily new cohort
Neurology Committee: CCSSNeurology Committee: CCSSAs of 2007:As of 2007:
R. Packer (chair)R. Packer (chair) CNMCCNMC NeurologyNeurologyG. Armstrong (coG. Armstrong (co--chair)chair) St. JudeSt. Jude OncologyOncologyD. BowersD. Bowers UT Southwestern(Dallas)UT Southwestern(Dallas) OncologyOncologyB. CohenB. Cohen Cleveland ClinicCleveland Clinic NeurologyNeurologyR. HayashiR. Hayashi Washington UniversityWashington University OncologyOncologyR. GoldsbyR. Goldsby Univ. of Calif. at San Fran.Univ. of Calif. at San Fran. OncologyOncologyA. KingA. King Washington UniversityWashington University OncologyOncologyB. MorrisB. Morris St. JudeSt. Jude NeurologyNeurologyA. ReddyA. Reddy Univ. of Alabama (Birmingham)Univ. of Alabama (Birmingham) NeurologyNeurologyC. TurnerC. Turner DFCCDFCC OncologyOncologyP. FisherP. Fisher StanfordStanford NeurologyNeurologyN. UllrichN. Ullrich Boston ChildrenBoston Children’’ss NeurologyNeurology
First Meeting: at COG 10/19/07First Meeting: at COG 10/19/07
Neurology Committee: IssuesNeurology Committee: Issues
Primary Focus on Brain TumorsPrimary Focus on Brain Tumors
Probably too limitedProbably too limitedLimited to data in survey (stroke; ? epilepsy; gross motor functLimited to data in survey (stroke; ? epilepsy; gross motor function; ion; neurosensory (hearing/vision/? Peripheral sensation)neurosensory (hearing/vision/? Peripheral sensation)Q of L, neuropsychological measures richer/easier to Q of L, neuropsychological measures richer/easier to ““minemine””Other diseases Other diseases -- 11°° leukemia understudiedleukemia understudiedLimited neuroscienceLimited neuroscience--oriented investigatorsoriented investigatorsNot focus of CCSS Not focus of CCSS –– more interventional/secondary tumors/more interventional/secondary tumors/
major health problemsmajor health problemsIs patient population representative of problems now Is patient population representative of problems now
Past ActivitiesPast Activities**
Gurney et al.Gurney et al. Endocrine/Cardiovasc. in BTEndocrine/Cardiovasc. in BT Cancer, 2003Cancer, 2003
Gurney et al.Gurney et al. Height and body Mass Index in BTHeight and body Mass Index in BT Cancer, 2003Cancer, 2003
Packer et al.Packer et al. Neurologic and Neurosensory in BTNeurologic and Neurosensory in BT JCO, 2003JCO, 2003
Zebrack et al.Zebrack et al. Psychological Outcomes in BTPsychological Outcomes in BT JCO, 2003JCO, 2003
Bowers et al.Bowers et al. Stroke in HodgkinsStroke in Hodgkins JCO, 2005JCO, 2005
Bowers et al.Bowers et al. Stroke in Leukemia / BTStroke in Leukemia / BT JCO, 2006JCO, 2006
Neglia et al.Neglia et al. Second CNS TumorsSecond CNS Tumors JNCI, 2006JNCI, 2006
Current ActivitiesCurrent Activities☺☺
ReorganizationReorganization
Multiple conference callsMultiple conference calls
First formal committee meeting 10/07First formal committee meeting 10/07
AnalysesAnalyses
““SurveySurvey”” study of B.T. near completion (study of B.T. near completion (ArmstrongArmstrong))
First First ““surveysurvey”” study of leukemia in analysis (study of leukemia in analysis (GoldsbyGoldsby))
Review of Review of ““Neurosensory ManuscriptsNeurosensory Manuscripts”” ((Whelan, Mertens, et al.)Whelan, Mertens, et al.)
Studies on Studies on ““BRIEFBRIEF”” being reportedbeing reported
Evaluation of sequelae of head and neck RT for Sarcomas(Ater)Evaluation of sequelae of head and neck RT for Sarcomas(Ater)
LongLong--term Neurologic Sequelae in Adult Survivors of term Neurologic Sequelae in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: Results from the Childhood Acute Lymphoblastic Leukemia: Results from the
Childhood Cancer Survivor StudyChildhood Cancer Survivor Study
Robert Goldsby, Paul Nathan, Daniel Bowers, Robert Goldsby, Paul Nathan, Daniel Bowers, Amanda YeatonAmanda Yeaton--Massey, Aimee Sznewajs, Massey, Aimee Sznewajs,
Les Robison, John Whitton, Lonnie Zeltzer, Les Robison, John Whitton, Lonnie Zeltzer, Greg Armstrong, Roger PackerGreg Armstrong, Roger Packer
>5 years after diagnosis
4.90;P=<.0001
5.12;P=<.0001
4.17;P=<.0001
2.44;P=0.0003
18.18;P=<.0001
1.85;P=0.0310
2.73;P=<.0001
1.73;P=<.0001
1.88;P=0.0396
RR§,_
2.82 - 4.012.69 - 3.853.72 - 5.070.59 - 1.192.23 - 3.290.40 - 0.922.39 - 3.472.18 - 3.220.31 - 0.7895% CI
3.383.234.360.852.720.632.892.660.50Rate‡
130124166341062511510520Yes
Any motorproblem
AnyCoordination
problem
DoubleVision
CataractsLegalBlindness inone or both
eyes
PersistentDizziness
TinnitusAny Hearingimpairment
Any SeizureDisorder
Focal Neurologic dysfunctionNeurosensory DeficitsConditions
Late-onset neurologic outcomes by exposure
Neurosensory Deficits Focal Neurologic Dysfunction Any Seizure Disorder
RR (95% CI) P-value RR (95% CI) P-value RR (95% CI) P-value
Cranial only 2.03 (0.18-22.37) 0.5636 1.48 (0.15-14.24) 0.7339 1.89 (0.35-10.33) 0.4616
Craniospinal 1.37 (0.28-6.59) 0.6947 1.15 (0.31-4.25) 0.8322 0.99 (0.31-3.17) 0.9923
Any cranial+IT 3.51 (0.87-14.12) 0.0774 3.38 (1.08-10.55) 0.0358 2.94 (1.10-7.88) 0.0318
IT alone 1.61 (0.39-6.66) 0.5126 1.72 (0.54-5.47) 0.3607 1.73 (0.63-4.71) 0.2850
None1.00 1.00 1.00
High dose MTX
Yes 1.22 (0.94-1.60) 0.1365 1.37 (1.11-1.70) 0.0040 1.50 (1.23-1.81) <.0001
No1.00 1.00 1.00
Recurrence
Yes 2.76 (2.18-3.50) <.0001 2.26 (1.84-2.77) <.0001 2.17 (1.80-2.61) <.0001
No1.00 1.00 1.00
LongLong--term Outcomes Among term Outcomes Among Survivors of CNS TumorsSurvivors of CNS Tumors
High risk for poor longHigh risk for poor long--term outcomes due to aggressive term outcomes due to aggressive surgery, RT & chemosurgery, RT & chemo
CCSS cohort includes 1,876 CNS tumor survivorsCCSS cohort includes 1,876 CNS tumor survivors1,233 Astrocytomas1,233 Astrocytomas395 Medulloblastoma/PNET395 Medulloblastoma/PNET148 Ependymoma148 Ependymoma
8 Major outcomes: mortality, SMN, health status, chronic 8 Major outcomes: mortality, SMN, health status, chronic conditions, education, employment, insurance, marital statusconditions, education, employment, insurance, marital status
LongLong--term Outcomes Among term Outcomes Among Survivors of CNS TumorsSurvivors of CNS Tumors
Analysis: assess outcomes by specific tumor Analysis: assess outcomes by specific tumor diagnoses, treatment type, and region specific diagnoses, treatment type, and region specific cumulative RT dosecumulative RT dose
Findings:Findings:Survival probability =74.2% @ 30 years Survival probability =74.2% @ 30 years RT associated w/ 3x risk of SMNRT associated w/ 3x risk of SMN
Platform presentation at ASCOPlatform presentation at ASCO
CCSSAn NCI-funded
ResourceSecond Neoplasms
9.1%
Years since diagnosis
Cum
ulat
ive
Inci
denc
e [%
]
5 10 15 20 25
0
2
4
6
8
10
12
14
16
Death
Second Neoplasms
Opportunities: FU2007 Opportunities: FU2007
Use 2007 to provide Use 2007 to provide ““10 Year Updates10 Year Updates”” including:including:1) 1) STROKESTROKE in Lymphoma/B.T. populations (aging in Lymphoma/B.T. populations (aging
population)population)2) 2) NEUROSENSORY DEFICITS NEUROSENSORY DEFICITS (update Packer paper) (update Packer paper) 3) Work with psychology committee to better define risk 3) Work with psychology committee to better define risk
factors involved in poor factors involved in poor neuropsychological/psychosocial outcomes in B.T. neuropsychological/psychosocial outcomes in B.T. survivorssurvivors
4) Evaluate across different tumor types frequency of 4) Evaluate across different tumor types frequency of ““SofterSofter”” neuro deficitsneuro deficits like like headaches/vertigoheadaches/vertigo and their and their impactimpact
Opportunities: FU2007Opportunities: FU2007
Using 2007 survey, secondary brain tumors are a major issueUsing 2007 survey, secondary brain tumors are a major issueIncreasing incidence of Increasing incidence of MENINGIOMASMENINGIOMAS their morbiditytheir morbidity
--SeizuresSeizures--HemiparesisHemiparesis--HeadachesHeadaches--(?Mortality)(?Mortality)
Are we picking up more Are we picking up more SECOND MALIGNANT CNS SECOND MALIGNANT CNS TUMORS?TUMORS?
--Where is the cross point between recurrence and Where is the cross point between recurrence and secondary tumors? secondary tumors?
Opportunities: ExpansionOpportunities: Expansion
Expansion of other cohort opportunities in addition to 1Expansion of other cohort opportunities in addition to 1ºº CNS populationCNS population
--Change in CNS Tumor managementChange in CNS Tumor management--decreased RT, increased chemodecreased RT, increased chemo
--Change in leukemia managementChange in leukemia management--Decreased CRTDecreased CRT--Increased intrathecals/systemic MTXIncreased intrathecals/systemic MTX
Wider use of Wider use of T.B.I./TransplantT.B.I./Transplant--StrokesStrokes--Neurocognitive DamageNeurocognitive Damage--LeukoencephalopathyLeukoencephalopathy--SpasticitySpasticity--HeadachesHeadaches--FatigueFatigue--Sleep DisturbanceSleep Disturbance
Opportunities: RFAOpportunities: RFARFARFA
Determination of Determination of MOLECULAR PREDISPOSITIONSMOLECULAR PREDISPOSITIONS to sequelae to sequelae in brain tumor/ALL/lymphoma/transplant survivors:in brain tumor/ALL/lymphoma/transplant survivors:
--Neurocognitive outcomeNeurocognitive outcome--Stroke (vascular complications)Stroke (vascular complications)--Neurosensory loss (platinum and/or RT associated Neurosensory loss (platinum and/or RT associated hearing loss, etc.)hearing loss, etc.)--SeizuresSeizures
NEUROLOGY QUESTIONAIRRENEUROLOGY QUESTIONAIRRE: high: high--risk populationsrisk populations--Incidence and severity of Incidence and severity of headachesheadaches--SeizureSeizure incidence and controlincidence and control--SleepSleep disruptiondisruption--Peripheral neuropathyPeripheral neuropathy(?)(?)--Telephone based assessment of Telephone based assessment of neurocognitive statusneurocognitive status(memory, attention, etc.)(memory, attention, etc.)
AimsAims
Determine the incidence of adverse neurologic conditions, Determine the incidence of adverse neurologic conditions, stratified by the time period in which the outcome was stratified by the time period in which the outcome was reported to first occur.reported to first occur.
Compare lateCompare late--onset (>5 years postonset (>5 years post--diagnosis) adverse diagnosis) adverse neurologic conditions among survivors to that of a group neurologic conditions among survivors to that of a group of participating siblings.of participating siblings.
Evaluate the effect of treatment on the risk of developing a Evaluate the effect of treatment on the risk of developing a late adverse neurologic condition.late adverse neurologic condition.
Neurology Committee:Long-term Priorities
1) Utilize DNA availability to determine “at risk” population
2) Work closely with Psychology Committee on BRIEF and other Q.O.L data
3) Major focus on new 1986+ cohort
- Major changes in B.T. / ? ALL management
- Reduction of RT (CSRT)
- Use of CPDD in B.T.
- Use of Alkylator / VP 16 in B.T. (? SMN)
- Cohort of “stem cell” survivors
Incidence Rates and Relative Risks by Time Period of Onset of Adverse Neurologic Outcomes
Neurosensory Deficits Focal Neurologic dysfunction
Any Hearingimpairment
Tinnitus PersistentDizziness
LegalBlindness inone or both
eyes
Cataracts DoubleVision
AnyCoordinatio
Problem
Any motorProblem
Reportedoutcome
Yes 56 145 143 46 181 65 314 267 253
1.36% 3.50% 3.45% 1.11% 4.38% 1.57% 7.64% 6.52% 6.15%
Any SeizureDisorder
Conditions
CCSSAn NCI-funded
ResourceSurvival by Primary Diagnosis
25 years:
Astro/Glial = 80.1%
Medullo/PNET = 75.2%
Ependymoma = 74.1%
p= .0003
All-Cause Mortality by Dx Type
Years since diagnosis
Surv
ival
pro
babi
lity
5 10 15 20 25
0.7
0.75
0.8
0.85
0.9
0.95
1astrocytoma/glial tumor
medulloblastoma/PNET
ependymomaSMRMedullo/PNET = 18.0Ependymoma = 15.9Astro/glial = 11.2
CCSSAn NCI-funded
Resource
Second Neoplasms
Years since diagnosis
Cum
ulat
ive
Inci
denc
e [%
]
5 10 15 20 25
02
46
810
12
SN other than NMSC+meningiomas
Meningiomas
NMSC
Death
3.8%
2.9%
CCSSAn NCI-funded
ResourceConclusions
• ↑ Late Mortality
– Largely due to recurrence
–↑ recurrence among males
• >9% develop a second neoplasm by 25y
• New medical conditions after 5y
• Poor health status
Table 2. Incidence Rates and Relative Risks by Time Period of Onset of Adverse Neurologic Outcomes
Neurosensory Deficits Focal Neurologic dysfunction
Conditions
Any Hearing
impairment
Tinnitus
Persistent Dizziness
Legal Blindness in one or both eyes
Cataracts
Double
Vision
Any coordination
problem
Any motor
problem
Any Seizure
Disorder
Any headache
Reported outcome
Yes
56 145 143 46 181 65 314 267 253 858
1.36% 3.50% 3.45% 1.11% 4.38% 1.57% 7.64% 6.52% 6.15% 20.98%
No
4065 3995 4003 4093 3951 4076 3796 3830 3860 3232
98.64% 96.50% 96.55% 98.89% 95.62% 98.43% 92.36% 93.48% 93.85% 79.02%
DX to 5 years
Yes 36 40 28 21 74 31 148 143 123 277
Rate‡ 1.75 1.94 1.36 1.02 3.61 1.50 7.36 7.15 6.09 14.12
95% CI 1.23 - 2.43 1.39 - 2.65
0.90 - 1.96
0.63 - 1.55
2.84 - 4.54
1.02 - 2.13
6.22 - 8.65 6.02 - 8.42
5.06 - 7.27
12.50 - 15.88
RR§,_ 4.53; P=<.0001
2.11; P=<.0001
2.40; P=<.0001
2.84; P=0.0004
20.62; P=<.0001
4.97; P=<.0001
7.40; P=<.0001
13.73; P=<.0001
6.15; P=<.0001
6.05; P=<.0001
95% CI 2.79 - 7.36 1.47 - 3.04
1.61 - 3.57
1.60 - 5.03
12.02 - 35.38
3.02 - 8.16
5.81 - 9.43 10.38 - 18.16
4.68 - 8.08
4.61 - 7.94
5 years after Dx
Yes 20 105 115 25 106 34 166 124 130 581
Rate‡ 0.50 2.66 2.89 0.63 2.72 0.85 4.36 3.23 3.38 16.70
95% CI 0.31 - 0.78 2.18 - 3.22
2.39 - 3.47
0.40 - 0.92
2.23 - 3.29
0.59 - 1.19
3.72 - 5.07 2.69 - 3.85
2.82 - 4.01
15.37 - 18.12
RR§,_ 1.88; P=0.0396
1.73; P=<.0001
2.73; P=<.0001
1.85; P=0.0310
18.18; P=<.0001
2.44; P=0.0003
4.17; P=<.0001
5.12; P=<.0001
4.90; P=<.0001
4.70; P=<.0001
95% CI 1.03 - 3.43 1.32 - 2.25
2.05 - 3.63
1.06 - 3.25
10.18 - 32.47
1.50 - 3.97
3.22 - 5.40 3.83 - 6.83
3.58 - 6.70
3.46 - 6.39
Abbreviation: RR, relative risk. *Excludes conditions prior to diagnosis. †Includes “not sure” and missing responses. ‡Rate per 1,000 person-years. §Adjusted for sex and age; relative to siblings. _P _ .0001.
Long-term Outcomes Among Survivors of Childhood
CNS Tumors:A Report from the Childhood Cancer Survivor Study
Greg Armstrong, Kirsten Ness, John Whitton, Wendy Leisenring, Qi Liu, Yutaka Yasui, Lonnie Zeltzer, Sarah Donaldson, Melissa
Hudson, Leslie Robison, Roger Packer
Department of Epidemiology and Cancer Control
CCSSAn NCI-funded
Resource Disclosure
I have no relationships to disclose
CCSSAn NCI-funded
ResourceBackground
• Modern therapy
–Surgery, RT & Chemotherapy
–↑ long-term survival–↑ potential for long-term morbidity &
late mortality
CCSSAn NCI-funded
ResourceStudy Objective
• Describe:– Long-term survival– Incidence of second neoplasms– Chronic medical conditions– Sociodemographic outcomes– Health status
Among adult survivors of childhood CNS tumors diagnosed 1970-1986
• Retrospective Cohort
• 5-Year Survival
• Diagnosis 1970-1986
• < 21 Yrs. At Diagnosis
• Detailed Treatment Data
• Wide Range of Outcomes
• 26 Contributing Centers
2,887 Eligible CNS TumorLost (n=491)
2,396 ContactedRefusal (n=511)
1,876 Participants: CNS Tumor
CCSSAn NCI-funded
ResourceStudy Overview
CCSS COHORTSelected Cancer Diagnosis
Consortium CenterDiagnosed 1970-1986
5-year Survival<21 yrs. At Diagnosis
English- or Spanish-Speaking
Treatment InformationMedical Record AbstractionRadiation Therapy Records
(RT Physics Center)
Pathology CenterConfirm Second NeoplasmsRepository - Second Cancers
Repository - Buccal Cell DNALCL for SMN Cases
National Death Index
Questionnaire / Interview DataSurvivors/ParentsSiblings
SIBLING COHORT
Random Sample
CCSSAn NCI-funded
Resource Study Overview
CCSSAn NCI-funded
ResourcePopulation
Survivors Siblings
Mortality 2,820 _
Second Neoplasms 1,876 _
Medical Conditions 1,876 3,899
Socio-demographic 1,032 2,358
Health Status 1,000 2,951
CCSSAn NCI-funded
ResourceParticipant Characteristics
N (%)
Female 843 (45)
Male 1033 (55)
Astro/glial 1233 (66)
Medullo/PNET 395 (21)
Ependymoma 148 (8)
Other 100 (5)
CCSSAn NCI-funded
ResourceParticipant Characteristics
N (%)Treatment Type
None 483 (30)1-49.9 Gy 278 (18)
Surgery only 438 (26)Surgery + RT 692 (42)Surgery + RT + Chemo 451 (27)Other 79 (5)
Cranial RT Dose
≥50 Gy 826 (52)
CCSSAn NCI-funded
ResourceOverall Survival (n = 546 deaths)
74.2%
98.5%
Years since diagnosis
Surv
ival
pro
babi
lity
[%]
5 10 15 20 25 30
70
75
80
85
90
95
100
U.S Population
CNS Tumor Population
CCSSAn NCI-funded
ResourceOverall Survival by Gender
Years since diagnosis5 10 15 20 25 30
70
75
80
85
90
95
100
Female
Male
US MaleUS Female
Sur
viva
l Pro
babi
lity
(%)
71.9%
99.6%
76.9%
98.0%
SMR:Male: 10.6 (9.5-11.8)Female: 19.6 (17.0-22.5)
Cause of DeathCCSSAn NCI-funded
ResourceCause of Death (n = 546 deaths)
N %Recurrence/Prog 335 61%Other Medical 112 21%
Second Neoplasm 51 9%Cardiac 17 3%Pulmonary 16 3%
External Causes 31 6%Unknown 68 12%
CCSSAn NCI-funded
ResourceCause Specific Mortality
Years since diagnosis
Cum
ulat
ive
inci
denc
e [%
]
5 10 15 20 25 30
0
2
4
6
8
10
12
14
RecurrenceSMNCardiacPulmonaryExternalOther
Cum
ulat
ive
Inci
denc
e (%
)
Years since diagnosis
14.0%
SMN=2.8%
Table 3. Late-onset neurologic outcomes by age, CNS therapy and chemotherapy exposures (Univariate analysis).
Neurosensory Deficits Focal Neurologic Dysfunction
Any Seizure Disorder Any headache
RR (95% CI)
P-value
RR (95% CI) P-value RR (95% CI)
P-value
RR (95% CI)
P-value
Age at Dx
<1 1.38 (0.50-3.84)
0.5330 1.98 (1.06-3.72)
0.0331 1.91 (1.07-3.39)
0.0283 2.26 (1.29-3.97)
0.0045
1-9 1.08 (0.80-1.48)
0.6114 0.88 (0.69-1.12)
0.2954 0.86 (0.70-1.07)
0.1770 0.91 (0.73-1.15)
0.4277
10+ 1.00 1.00 1.00 1.00
Cranial radiation
Unknown 3.03 (0.74-12.43)
0.1245 2.93 (0.92-9.29)
0.0678 2.46 (0.90-6.71)
0.0784 3.14 (0.99-9.95)
0.0522
Cranial only 2.03 (0.18-22.37)
0.5636 1.48 (0.15-14.24)
0.7339 1.89 (0.35-10.33)
0.4616 3.34 (0.56-19.98)
0.1866
Craniospinal 1.37 (0.28-6.59)
0.6947 1.15 (0.31-4.25)
0.8322 0.99 (0.31-3.17)
0.9923 1.58 (0.45-5.60)
0.4788
Any cranial+IT 3.51 (0.87-14.12)
0.0774 3.38 (1.08-10.55)
0.0358 2.94 (1.10-7.88)
0.0318 3.96 (1.27-12.34)
0.0176
IT alone 1.61 (0.39-6.66)
0.5126 1.72 (0.54-5.47)
0.3607 1.73 (0.63-4.71)
0.2850 2.28 (0.72-7.24)
0.1619
None 1.00 1.00 1.00 1.00
Cranial XRT dose
Unknown 1.87 (1.23-2.84)
0.0032 1.74 (1.24-2.44)
0.0013 1.41 (1.03-1.91)
0.0295 1.44 (1.04-2.01)
0.0290
>18 Gy 1.96 (1.38-2.78)
0.0002 1.88 (1.42-2.49)
<.0001 1.64 (1.29-2.09)
<.0001 1.70 (1.31-2.21)
<.0001
0.1-18 Gy 2.33 (1.61-3.39)
<.0001 1.94 (1.43-2.63)
<.0001 1.71 (1.31-2.24)
<.0001 1.82 (1.37-2.42)
<.0001
None 1.00 1.00 1.00 1.00
High dose IV MTX
Unknown 1.00 (0.70-1.42)
0.9985 1.08 (0.81-1.44)
0.5814 1.10 (0.84-1.43)
0.5001 1.06 (0.81-1.41)
0.6599
Yes 1.22 (0.94-1.60)
0.1365 1.37 (1.11-1.70)
0.0040 1.50 (1.23-1.81)
<.0001 1.49 (1.22-1.82)
<.0001
No 1.00 1.00 1.00 1.00
MTX cumulative non-IT dose
Unknown 1.06 (0.74-1.52)
0.7499 1.22 (0.91-1.64)
0.1876 1.20 (0.92-1.58)
0.1817 1.18 (0.89-1.57)
0.2576
5000.1+ mg/m2 1.20 (0.80-1.78)
0.3737 1.50 (1.09-2.05)
0.0119 1.60 (1.21-2.11)
0.0009 1.54 (1.14-2.06)
0.0044
1501-5000 mg/m2 1.44 (1.02- 0.0374 1.63 (1.22- 0.0009 1.70 (1.32- <.0001 1.78 (1.37- <.0001
CCSSAn NCI-funded
Resource Death Due to Recurrence
Years since diagnosis
Cum
ulat
ive
inci
denc
e [%
]
5 10 15 20 25 30
0
2
4
6
8
10
12
14
16
Male
Female
15.6%
12.1%
P=.049
CCSSAn NCI-funded
ResourceDeath from Recurrence
Primary Diagnosis
AnnualRate (%)
p value
Astro/glial .64 <.001
Medullo/PNET 1.15
Ependymoma 1.26
CCSSAn NCI-funded
Resource Survival by Primary Diagnosis
5 10 15 20 25 30
70
75
80
85
90
95
100
Astro/glial
EpendymomaMedullo/PNET
SMR:Medullo/PNET: 18.0Ependymoma: 15.9Astro/glial: 11.2
Surv
ival
Pro
babi
lity
(%)
P = .003
CCSSAn NCI-funded
ResourceSecond Neoplasms
9.1%
Years since diagnosis
Cum
ulat
ive
Inci
denc
e [%
]
5 10 15 20 25
0
2
4
6
8
10
12
14
16
Death
Second Neoplasms
CCSSAn NCI-funded
ResourceSecond Neoplasms
N
Total 223
Non-MalignantMeningiomas
Malignant
53
Non-melanoma skin 100Other SMNs 70
CCSSAn NCI-funded
ResourceSecond Malignant Neoplasms
Obs. Exp. SIR(95%CI)
All SMNs 70 18.5
0.8
1.0
Thyroid 12 1.1 11.2 (5.4-18.2)
Leukemia 3 0.7 4.1 (1.1-16.3)
Other 29 - -
3.8 (0.2-0.3)
CNS malignancies 14 17.8 (12.3-37.9)
Soft-tissue Sarcoma 12 12.5 (6.7-22.6)
CCSSAn NCI-funded
ResourceSecond Neoplasms
3.8%
2.9%
Years since diagnosis
Cum
ulat
ive
Inci
denc
e [%
]
5 10 15 20 25
0
2
4
6
8
10
12
SN other than NMSC+meningiomas
Meningiomas
NMSC
Death
CCSSAn NCI-funded
Resource Second Neoplasms by RT dose
4.5%
8.6%
12.2%
5 10 15 20 250
2
4
6
8
10
12
14
Cum
ulat
ive
Inci
denc
e (%
)
Years since diagnosis
No RT
1-49 Gy
≥50 Gy
p <0.001
CCSSAn NCI-funded
Resource
Chronic Health Conditions: Incidence after 5 years
CumulativeIncidence (%)
Rate Ratio (95% CI)
Endocrine (any) 32.223.1
19.07.3
72.432.951.615.5
19.8 (14.5-27.1)-GH deficiency 140.4 (51.3-384.1)
-Hypothyroidism 13.0 (9.2-18.3)Musculoskeletal 13.8 (7.4-25.7)Neurological (any) 5.6 (4.8-6.7)
-Seizure 15.1 (10.7-21.2)-Balance 18.0 (13.4-24.1)- Blindness 7.5 (4.1-13.5)
CCSSAn NCI-funded
ResourceSocio-economic Outcomes
Survivors%
Sibs%
Odds Ratio (95%CI)*
High School Graduate
91 99 3.7 (2.5-5.5)
Married 33 69 4.3 (3.7-5.1)
Employed 67 94 12.0 (9.1-15.8)
Insured 88 91 1.1 (.8-1.4)
Income >20,000 76 93 3.7 (2.9-4.8)
* Adjusted for age, sex and intra-family correlation
CCSSAn NCI-funded
ResourceHealth Status
Survivors%
Sibs%
Odds Ratio (95%CI)*
Poor General Health
53 17 22.5 (14.3-35.3)
Poor Mental Health
21 14 1.4 (1.2-1.7)
Poor Functional Status
38 3 25.9 (18.9-35.4)
Poor Activity Level
19 0.6 39.5 (22.7-68.7)
Pain 10 1 7.6 (4.9-11.8)Anxiety 8 1 10.0 (6.2-16.2)
*Adjusted for age at interview, sex, ethnicity, education, income and health insurance
CCSSAn NCI-funded
ResourceConclusions
• High Risk for Late Mortality– >25% at 30 years
– Largely due to recurrence
• >9% develop a second neoplasm by 25y
• New medical conditions after 5y
• Poor health status